The aim is to gain knowledge of the cell membrane-associated contractile and cytoskeletal apparatus, and the differences in organization of this apparatus in normal and in transformed (cancer) cells. Because cytochalasins selectively and reversibly affect this system, in a major part of this study cytochalasins, especially cytochalasin D (CD), will be used as a probe of the membrane-associated contractile structures and their interrelations. The influence of treatments that act in defined ways on cell membrane; on microfilament apparatus and cytoskeletal structures will be studied by examining the structure, filament distribution and 3H-CD uptake of treated cells or fractions, in comparison with the effects of CD. We will especially compare nontransformed and the transformed (including epithelial) cells derived from them with respect to binding of 3H-CD their microfilament apparatus, and the differential effects of CD treatment on their membrane-associated contractile structures and on their behavior. In the ensuing period we propose to examine the action of cytochalasins and related agents in gels and cytoskeletal models morphologically, immunocytologically and electrophoretically. We propose to examine the differences in arrangements of the contractile and cytoskeletal strutures in nontransformed and transformed cell pairs and their different responses to cytochalasin. The process of cytochalasin-induced capping will be studied with special reference to the role of 10 nm filaments and microtubules. We propose to investigate the basis for differences in the effects and for differental cytotoxicity of CD in normal cells and those exhibiting unregulated growth (cancer cells), as well as the selective lethality of combined cytochalasin and carcinostatic drug for cancer cells.